scholarly journals Reg3α and Reg3β Expressions Followed by JAK2/STAT3 Activation Play a Pivotal Role in the Acceleration of Liver Hypertrophy in a Rat ALPPS Model

2020 ◽  
Vol 21 (11) ◽  
pp. 4077
Author(s):  
Naohiko Otsuka ◽  
Masato Yoshioka ◽  
Yuki Abe ◽  
Yasuhiko Nakagawa ◽  
Hiroshi Uchinami ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Regeneration ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Janus Kinase ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Regeneration Rate ◽  
Stat3 Pathway ◽  
Cytokine Levels

To explore the underlying mechanism of rapid liver hypertrophy by liver partition in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), liver partition at different sites was investigated. Increased inflammatory cytokines owing to the liver partition have been reportedly responsible. If this were true, rapid liver hypertrophy should be achieved regardless of where the liver was split. A male Sprague-Dawley rat model was created, in which a liver split was placed inside the portal vein ligated lobe (PiLL), in addition to the ALPPS and portal vein ligation (PVL) models. Liver regeneration rate, inflammatory cytokine levels, activation status of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and expressions of regenerating islet-derived (Reg)3α and Reg3β were investigated. The liver regeneration rate was significantly higher in the ALPPS group than in the PiLL group, whereas inflammatory cytokine levels were nearly equal. Additional volume increase in ALPPS group over PVL and PiLL groups was JAK2/STAT3-dependent. Reg3α and Reg3β expressions were observed only in the ALPPS group. An increase in inflammatory cytokines was not enough to describe the mechanism of rapid liver hypertrophy in ALPPS. Expressions of Reg3α and Reg3β could play an important role in conjunction with an activation of the JAK2/STAT3 pathway.

scholarly journals Corosolic Acid Inhibits Tumor Growth without Compromising ALPPS-induced Liver Regeneration in Rats

2020 ◽  
Author(s):  
Jinwei zhao ◽  
xueyue luo ◽  
weiyi zhao ◽  
hong zhou ◽  
hongyue xu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Liver Regeneration ◽  
Macrophage Polarization ◽  
Hepatic Regeneration ◽  
M2 Macrophage ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Regeneration Rate ◽  
Sprague Dawley Rats ◽  
Corosolic Acid

Abstract BackgroudThe associating liver partition and portal vein ligation (ALPPS) technique is a promising strategy for unresectable tumors without sufficient future liver remnants (FLRs). Criticism has focused on its stimulation of tumor growth. This study explores the effect of corosolic acid (CA) on inhibiting tumor growth without compromising ALPPS-induced liver regeneration and investigates its possible mechanism.MethodsThe ALPPS procedure was performed in Sprague-Dawley rats with orthotopic liver cancer. Blood, tumor and FLR samples in different group were collected.ResultsThe tumor weight in the implantation/ALPPS/CA group was lower than that in the implantation/ALPPS group (p < 0.05). On postoperative day 15, the hepatic regeneration rate and the expression of Ki67+ hepatocytes in the FLRs increased significantly in the group that underwent ALPPS. The number of CD86+ macrophages increased in the FLRs and tumors of the groups that underwent the ALPPS procedure. Additionally, the number of CD206+ macrophages was higher than the number of CD86+ macrophages in the tumors of the implantation group and the implantation/ALPPS group (p < 0.01, respectively); however, the opposite results were observed in the CA groups. The administration of CA downregulated the expression of TGF-β, CD31 and PD-1, whereas it increased the number of CD8+ lymphocytes in tumors.ConclusionsCA inhibits tumor growth without compromising ALPPS-induced liver regeneration. This result may be attributed to the CA-induced downregulation of PD-1 and TGF-β expression and the increased CD8+ lymphocyte infiltration in tumor tissue, associated with the suppression of M2 macrophage polarization.

scholarly journals The Role of Farnesoid X Receptor in Accelerated Liver Regeneration in Rats Subjected to ALPPS

2021 ◽  
Vol 28 (6) ◽  
pp. 5240-5254
Author(s):  
Noemi Daradics ◽  
Pim B. Olthof ◽  
Andras Budai ◽  
Michal Heger ◽  
Thomas M. van Gulik ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Regeneration ◽  
Farnesoid X Receptor ◽  
Signaling Cascades ◽  
Portal Vein Ligation ◽  
Mrna Levels ◽  
Hemodynamic Changes ◽  
Regeneration Rate ◽  
Male Wistar Rats

Background: the role of bile acid (BA)-induced farnesoid X receptor (Fxr) signaling in liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was investigated in a rat model. Methods: Male Wistar rats underwent portal vein ligation (PVL) (n = 30) or ALPPS (n = 30). Animals were sacrificed pre-operatively and at 24, 48, 72, or 168 h after intervention. Regeneration rate, Ki67 index, hemodynamic changes in the hepatic circulation, and BA levels were assessed. Transcriptome analysis of molecular regulators involved in the Fxr signaling pathway, BA transport, and BA production was performed. Results: ALLPS induced more extensive liver regeneration (p < 0.001) and elevation of systemic and portal BA levels (p < 0.05) than PVL. The mRNA levels of proteins participating in hepatic Fxr signaling were comparable between the intervention groups. More profound activation of the intestinal Fxr pathway was observed 24 h after ALPPS compared to PVL. Conclusion: Our study elaborates on a possible linkage between BA-induced Fxr signaling and accelerated liver regeneration induced by ALPPS in rats. ALPPS could trigger liver regeneration via intestinal Fxr signaling cascades instead of hepatic Fxr signaling, thereby deviating from the mechanism of BA-mediated regeneration following one-stage hepatectomy.

scholarly journals Effect of Portal Vein Ligation Plus Venous Congestion on Liver Regeneration in Rats

2019 ◽  
Vol 18 (1) ◽  
pp. 89-100
Author(s):  
Daisuke Kawaguchi ◽  
Yukihiko Hiroshima ◽  
Takafumi Kumamoto ◽  
Ryutaro Mori ◽  
Ryusei Matsuyama ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Regeneration ◽  
Venous Congestion ◽  
Portal Vein Ligation

95 N-Acetyl cysteine as a potential treatment for equine persistent breeding-induced endometritis

2019 ◽  
Vol 31 (1) ◽  
pp. 173
Author(s):  
M. Caissie ◽  
T. Chenier ◽  
C. Gartley ◽  
E. Scholtz ◽  
R. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Clinical Trial ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Clinical Signs ◽  
Time Points ◽  
Cytokine Levels ◽  
Uterine Inflammation ◽  
Endometrial Cytology

Persistent breeding-induced endometritis (PBIE) is a major cause of infertility in mares. Transient uterine inflammation is a normal response to breeding; however, PBIE-susceptible mares do not clear this inflammation in a timely fashion. Uterine inflammation at the time of embryonic descent from the oviducts ultimately results in early embryonic death and is seen clinically as infertility. Several risk factors for PBIE have been identified and include age, parity, anatomical conformation, such as poor perineal conformation and cervical fibrosis, as well as other reproductive tract abnormalities. N-Acetyl cysteine (NAC), a mucolytic used to treat endometritis in mares, has anti-inflammatory properties, affects inflammatory cytokines, and is a mild inhibitor of nitric oxide synthase. Increased nitric oxide, causing smooth muscle relaxation and alterations in inflammatory cytokines, has been documented in PBIE mares. The objective of our study was to determine if NAC treatment would lower nitric oxide and inflammatory cytokine levels, thereby resolving PBIE. A randomised, blinded, crossover design clinical trial was performed utilising PBIE-susceptible mares (n=10). Mares were screened for bacterial endometritis before enrolment in the study and only mares that had negative bacterial cultures were used. No other treatments were given to mares while they were enrolled in the study. Intrauterine infusion of 180mL of 3.3% NAC was performed 12h before insemination, when a follicle &gt;35mm was present. Mares were sampled for endometrial cytology and endometrial fluid to determine inflammatory cytokine (ELISA) and nitric oxide (colourimetric assay) levels at 12 and 72h post-insemination. Endometrial biopsies were taken at the same time points post-insemination to determine gene expression of inflammatory cytokines by qPCR. Clinical signs of endometrial oedema and intrauterine fluid volumes were assessed at 12 and then every 24h post-breeding. Statistical assessment of the data was performed using a repeated-measures ANOVA. Uterine inflammation, as determined by percent number of neutrophils on endometrial cytology (P=0.0006), and interleukin 6 gene expression (P=0.003) were highest at 12h. Uterine oedema was greatest at 12 and 24h (P=0.02) and uterine fluid volumes were highest at 24h (P=0.02). Interestingly, interleukin-6 protein levels were not in accordance with gene expression, and were highest at 72h. In this clinical trial, pre-breeding intrauterine treatment with NAC did not affect nitric oxide levels, cytokine gene expression, or clinical signs of PBIE. However, the pattern of inflammation noted in this study is consistent with that described in PBIE mares. Nevertheless, the assessment of inflammatory cytokines, both at the gene and protein level at different time points post-AI, in combination with clinical signs will add to the understanding of the alterations in inflammatory cytokine levels in mares susceptible to PBIE.

scholarly journals Standardization of experimental microsurgical model of ALPPS (Associating liver portal vein ligation partition and staged for hepatectomy) in Sprague Dawley rats

HPB ◽  
2017 ◽  
Vol 19 ◽  
pp. S114
Author(s):  
C. Mandiola ◽  
M. Zapata ◽  
R. Vargas ◽  
S. Uribe-Echevarraa ◽  
M. Uribe ◽  
...  
Keyword(s):  
Portal Vein ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Effects of endothelin in portal hypertensive rats

1992 ◽  
Vol 83 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Pi-Chin Yu ◽  
Jon-Son Kuo ◽  
Han-Chieh Lin ◽  
May C. M. Yang
Keyword(s):  
Blood Pressure ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Venous Pressure ◽  
Portal Venous Pressure ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Endothelin 1 ◽  
Sprague Dawley Rats

1. Effects of endothelin-1 on systemic arterial blood pressure, heart rate and portal venous pressure were compared in normal Sprague-Dawley rats and rats with portal hypertension induced by CCl4 and partial portal vein ligation. 2. Endothelin-1 produced biphasic effects on systemic blood pressure and portal venous pressure in all three groups of rats. However, the magnitude of the changes in blood pressure was less in portal hypertensive rats. 3. The ability of endothelin-1 to increase the portal venous pressure was also significantly diminished in portal hypertensive rats. On the other hand, the initial decrease in portal pressure was augmented in rats with partial portal vein ligation, and disappeared at higher dosage in CCl4-treated rats. 4. In accordance with the pressure recording in vivo, the dose-response vasoconstrictive activity of endothelin-1 was significantly attenuated in the intrahepatic vasculature. 5. The plasma immunoreactive endothelin concentration was significantly higher (5.55 ± 0.81 fmol/ml) in Sprague-Dawley rats than in CCl4-treated rats (2.83 ± 0.56 fmol/ml) and rats with partial portal vein ligation (2.68 ± 0.53 fmol/ml). 6. It was concluded that a lower plasma level of endothelin and a reduced vascular responsiveness may contribute, at least in part, to the hyperdynamics of portal hypertension.

Ischemia/Reperfusion in Clamped Lobes Facilitates Liver Regeneration of Non-clamped Lobes After Selective Portal Vein Ligation

2012 ◽  
Vol 57 (12) ◽  
pp. 3178-3183 ◽  
Author(s):  
Jian-hua Yu ◽  
Wei-guang Zhang ◽  
Gui-xing Jiang ◽  
Jia-yun Zhao ◽  
Hui Li ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Regeneration ◽  
Ischemia Reperfusion ◽  
Portal Vein Ligation

scholarly journals Transection of the hepatic parenchyma associated or not with the contralateral portal vein branch ligature and its effect in liver regeneration

2017 ◽  
Vol 15 (2) ◽  
pp. 178-185
Author(s):  
Henrique de Aguiar Wiederkehr ◽  
Julio Cesar Wiederkehr ◽  
Luiz Martins Collaço ◽  
Eros Luiz de Sousa ◽  
Paolo Salvalaggio ◽  
...  
Keyword(s):  
Liver Resection ◽  
Portal Vein ◽  
Liver Regeneration ◽  
Inflammatory Cells ◽  
Hepatic Regeneration ◽  
Portal Vein Ligation ◽  
Portal Vein Branch ◽  
Regeneration Status ◽  
Left Portal Vein ◽  
Two Stages

ABSTRACT Objective To analyze the influence of portal vein ligation in hepatic regeneration by immunohistochemical criteria. Methods Ten pigs divided into two groups of five animals underwent hepatectomy in two stages, and the groups were differentiated by ligation or not of the left portal vein tributary, which is responsible for vascularization of the left lateral and medial lobes of the pig liver. Five days after the procedure, the animals underwent liver biopsies for further analysis of histological and immunohistochemical with marker Ki67. Results The group submitted to hepatectomy with vascular ligation showed an increase of approximately 4% of hepatocytes in regeneration status, as well as a greater presence of Kupffer and inflammatory cells as compared to control. Conclusion As a result of positive cell replication observed through the Ki67 marker, we can suspect that the ligation of a tributary of the portal vein associated with liver resection promoted a greater stimulus of liver regeneration when compared to liver resection alone.

scholarly journals Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 371
Author(s):  
Jorge Gutiérrez Sáenz de Santa María ◽  
Borja Herrero de la Parte ◽  
Gaizka Gutiérrez-Sánchez ◽  
Inmaculada Ruiz Montesinos ◽  
Sira Iturrizaga Correcher ◽  
...  
Keyword(s):  
Liver Function ◽  
Portal Vein ◽  
Liver Regeneration ◽  
Folinic Acid ◽  
Hepatic Metastases ◽  
Future Liver Remnant ◽  
Control Group ◽  
Portal Vein Ligation ◽  
Nuclear Area ◽  
Liver Remnant

Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child–Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm2, and 49.91 ± 15.38 µm2; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL.

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